Introduction: Moderate-to-severe ulcerative colitis (UC) is commonly treated with oral corticosteroids. However, in cases of oral corticosteroid failure, no clear consensus exists on whether to transition to intravenous corticosteroids (IVCS) or initiate advanced therapies. The aim of this study was to evaluate whether responsiveness to oral corticosteroids is associated with differences in the efficacy of IVCS. Methods: This multicenter cohort study (conducted at 10 facilities) included patients with moderate-to-severe UC who were transitioned to IVCS after failure of oral corticosteroid therapy. The patients were categorized into the partial responder and nonresponder groups based on their response to oral corticosteroids, as measured by improvements in their PRO-2 scores. The primary outcome was clinical remission at day 30, defined as a total PRO-2 score ≤1 with a rectal bleeding subscore of 0. Logistic regression was used to estimate the odds ratio (OR) of achieving clinical remission. Results: A total of 123 patients with UC were included, with 41 and 82 patients in the partial responder and nonresponder groups, respectively. Clinical remission at day 30 was achieved in 41.4% of the partial responders and 18.3% of the nonresponders (multivariable-adjusted OR, 0.35 [95% CI: 0.15–0.83]; p = 0.017). The nonresponder group had a higher risk of requiring advanced therapies within 90 days than the partial responder group (multivariable-adjusted OR, 2.48 [95% CI: 1.09–5.66]; p = 0.030). Conclusions: In patients with UC and oral corticosteroid failure, responsiveness to oral corticosteroids may be associated with differences in IVCS efficacy.

Introduction: Upadacitinib (UPA), a Janus kinase inhibitor approved for the treatment of Crohn’s disease (CD), has demonstrated high efficacy in clinical trials; however, real-world data on its outcomes remain limited. This study evaluated UPA outcomes in patients with CD in a real-world setting. Methods: We retrospectively analyzed patients who initiated UPA treatment between June 2023 and June 2024. The primary endpoints were clinical response and remission at 12 and 54 weeks. The secondary endpoints included changes in the C-reactive protein (CRP) levels, serum albumin levels, and perianal fistula response. Results: Thirteen patients (mean age, 32.0 years; 92.3% male; mean disease duration, 114.1 months) were included. At baseline, three (23.1%) patients used oral corticosteroids, and 11 (84.6%) had undergone prior biologic therapy, with nine (81.8%) exposed to anti-tumor necrosis factor-alpha antibodies. The mean follow-up period was 53.1 weeks, and the 54-week continuation rate was 83.3%. The clinical response rates were 46.2% and 53.8%, and the remission rates were 69.2% and 84.6% at 12 and 54 weeks, respectively. The mean Crohn’s Disease Activity Index scores decreased from 226.8 at baseline to 73.7 at 54 weeks, and the average CRP and albumin levels improved correspondingly. Among the 7 patients (53.8%) with draining perianal fistulas, six (85.7%) achieved cessation of pus discharge by week 8 (mean, 4.4 weeks). No significant adverse events were observed. Conclusion: UPA appears to be an effective treatment for CD and may facilitate the early resolution of perianal fistulas, supporting its role in managing perianal disease.

Introduction: De novo inflammatory bowel disease (IBD) is a rare but clinically significant complication after solid organ transplantation (SOT), with incidence higher than that in the general population. Its pathogenesis, diagnostic challenges, and optimal management remain poorly defined. We describe 6 cases of de novo IBD following liver or heart transplantation and evaluate therapeutic outcomes with selective biologics targeting the IL-23 pathway. Methods: Six SOT recipients (3 liver, 3 heart) developed new-onset ulcerative colitis-type (UC-type, n = 3) or Crohn’s disease-like (CD-like, n = 3) IBD after a median of 47.5 months post-transplantation. None had pre-transplant intestinal symptoms; colonoscopy was negative before transplantation in 2 UC-type cases. Alternative etiologies – including cytomegalovirus colitis, drug-induced colitis, and post-transplant lymphoproliferative disorder – were rigorously excluded. Treatments included systemic corticosteroids, mirikizumab, ustekinumab, or risankizumab. Median follow-up was 15.6 months. Results: Corticosteroids induced remission in 2 UC-type cases, while one steroid-refractory UC-type case and all CD-like cases achieved clinical improvement and endoscopic response or remission with IL-23-targeted biologics. No opportunistic infections, severe biologic-related adverse events, or graft rejection were observed. Conclusions: De novo IBD emerged years after SOT, with variable phenotypes despite baseline immunosuppression. IL-23 pathway inhibitors demonstrated favorable efficacy and safety in this vulnerable population, representing a promising strategy warranting further prospective evaluation.

Karger Publishers and the editors of Inflammatory Intestinal Diseases would like to thank the reviewers for their ongoing support in reviewing manuscripts for our Journal in 2025. This year we have chosen not to disclose the names of our reviewers to preserve the principle of anonymity inherent to the single-blind peer-review we follow. Even so, this should not be in our way to sincerely thank all contributing reviewers who have volunteered their time, effort, and expertise in benefit of the quality of the manuscripts we received and published in 2025. Individual reviewers can still claim their personal “Certificate of Review” via the Journal’s manuscript submission system.

Plain Language SummaryThis report assessed the long-term efficacy and safety of ustekinumab (UST) in Asian patients with moderate to severe ulcerative colitis (UC). Patients completed 44 weeks of UST maintenance treatment and continued UST treatment in this long-term extension (LTE) study (duration week 44 to week 220). Patients received UST 90 mg under the skin every 8 weeks (q8w) or every 12 weeks (q12w). The objective was to determine if patients’ disease symptoms (e.g., stool frequency and rectal bleeding) would sustain their response to UST and/or achieve remission (i.e., symptomatic remission). Forty-one patients were enrolled. In both treatment groups, reduced disease symptoms were maintained through week 200, indicating symptomatic remission (UST 90 mg SC q12w, 62.5% of patients; UST 90 mg SC q8w, 37.9%). At week 200, most patients were not taking corticosteroids to manage their disease, indicating corticosteroid-free symptomatic remission (UST 90 mg SC q12w, 78.9%; UST 90 mg SC q8w, 50.0%). The observed Mayo clinical remission/response rates were 58.8%/94.1% and 75.0%/100.0% in UST 90 mg SC q12w and q8w groups, respectively. Most patients also demonstrated endoscopic healing at week 200 (UST 90 mg SC q12w, 70.6%; UST 90 mg SC q8w, 91.7%). Despite the small sample size which limited data interpretation, the efficacy and safety of UST treatment were sustained during the LTE and provided clinical benefits to Asian patients with UC. Asian patients with relatively stable clinical condition may benefit from a UST 90 mg SC q12w treatment regimen, given its sustained efficacy and low discontinuation rates.

Introduction: 5-Aminosalicylic acid (5-ASA, mesalamine) is the cornerstone for maintaining remission in mild-to-moderate ulcerative colitis (UC), with several formulations available. Nonadherence to mesalamine is associated with increased relapse risk; however, large-scale real-world data comparing adherence and relapse among different formulations remain limited. This study aimed to evaluate adherence and relapse risk among four 5-ASA formulations using a large Japanese healthcare database. Methods: Using a Japanese nationwide claims database, we retrospectively analyzed UC patients who were prescribed any of four oral 5-ASA formulations – time-dependent mesalamine, pH-dependent mesalamine, multi-matrix system (MMX) mesalamine, or salazosulfapyridine – between 2008 and 2022. Adherence was assessed using the proportion of days covered (PDC), and relapse was defined as UC-related hospitalization or escalation of therapy. A Cox proportional hazards model was used to identify factors associated with relapse. Results: Among 13,876 eligible patients, MMX mesalamine showed the highest adherence (mean PDC: 91.6%) and the lowest relapse rate (2.9%), while salazosulfapyridine had the highest relapse rate (14.8%). In multivariate analysis, pH-dependent mesalamine (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.51–0.72) and MMX mesalamine (HR, 0.53; 95% CI, 0.35–0.78) significantly reduced relapse risk compared to time-dependent mesalamine, whereas salazosulfapyridine (HR, 1.51; 95% CI, 1.32–1.73) significantly increased relapse risk. Conclusion: MMX mesalamine was associated with the highest adherence and lowest relapse rates among the four 5-ASA formulations. These findings emphasize the importance of formulation choice in UC management.

Introduction: Upadacitinib and tofacitinib, oral Janus kinase inhibitors, have demonstrated efficacy and safety in ulcerative colitis (UC) in clinical trials. However, real-world comparative data are limited. We conducted a systematic review and meta-analysis of studies directly comparing upadacitinib to tofacitinib in UC management. Methods: We conducted a systematic search of multiple databases through August 2025 for studies comparing upadacitinib and tofacitinib for UC management. The primary outcome was steroid-free clinical remission (SFCR) at weeks 8–14. Secondary outcomes included SFCR at later timepoints, clinical and endoscopic remission, biochemical remission, treatment discontinuation, colectomy, and safety. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effects model. Heterogeneity was assessed using the I2% statistic. Results: Ten retrospective studies with 2,021 patients (879 upadacitinib and 1,142 tofacitinib) were analyzed. Upadacitinib was associated with significantly higher SFCR at weeks 8–14 (OR 1.98; 95% CI: 1.32–3.97; I2 = 30%), 48–60 weeks (OR 2.32; 95% CI: 1.50–3.58; I2 = 0%), and at the end of study follow-up (OR 3.60; 95% CI: 1.73–3.92; I2 = 0%). Rates of endoscopic and biochemical remission did not differ significantly. Treatment discontinuation was less frequent with upadacitinib (OR 0.51; 95% CI: 0.34–0.77; I2 = 22%). Overall safety was comparable, except for higher odds of acne with upadacitinib (OR 4.30; 95% CI: 1.86–9.95; I2 = 0%). Conclusion: Upadacitinib may be more effective than tofacitinib in achieving and sustaining SFCR, with better treatment persistence and similar overall safety. Larger, prospective head-to-head trials are needed to validate these findings.

Background: Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is a chronic lifelong condition that affects the colon to a variable extent. Current treatments for IBD include aminosalicylate-based drugs, corticosteroids, antibiotics, immunomodulators, biologics, other small-molecule drugs, and surgical intervention. Nonetheless, treatment options are variably effective, associated with serious side effects, and often leave individuals at risk of relapse. Summary: In this narrative review, we explore emu oil (EO), a naturally sourced agent, that may be utilised to broaden therapeutic options in IBD. The anti-inflammatory, antioxidant, reparative, and protective properties of EO have been attributed to its unique blend of fatty acids and non-triglyceride fraction. To date, several preclinical trials of orally administered EO have demonstrated these properties in a range of intestinal inflammatory conditions, showing reduced inflammation and mucosal damage, together enhancing intestinal healing. Key Messages: While EO remains an interesting candidate for future investigations, current knowledge is limited to animal models and its clinical relevance is yet to be defined. Well-designed clinical trials will be essential to determine the safety and efficacy of EO before it can be considered as a potential adjunct to conventional therapy for IBD.

Introduction: Serum leucine-rich alpha-2 glycoprotein (LRG) has emerged as a novel biomarker for inflammatory bowel disease (IBD). However, its clinical utility among non-Japanese populations has not been investigated. This study aimed to validate the diagnostic ability of serum LRG in non-Japanese patients with IBD. Methods: A retrospective cross-sectional study was conducted, including patients with IBD who underwent at least one serum LRG measurement between 2020 and 2023. Correlations between serum LRG and C-reactive protein (CRP) levels were independently evaluated in Japanese and non-Japanese cohorts. The association between endoscopic activity and serum LRG levels was investigated, and the diagnostic performance of LRG for detecting endoscopic activity was evaluated using receiver operating characteristic (ROC) analysis. Results: Serum LRG levels were measured at 11,730 time points for 2,500 Japanese patients and 276 time points for 58 non-Japanese patients. Among non-Japanese patients, 53% were Asian, 37% White, 4% Black, and 6% other racial backgrounds. The correlation between LRG and CRP was similarly robust in non-Japanese (r = 0.64) and Japanese (r = 0.64) patients. Among non-Japanese, serum LRG levels in endoscopic remission were significantly lower than those in active disease (p = 0.0228). The area under the ROC curve of LRG for endoscopically active disease in ulcerative colitis (n = 46) was 0.79 (95% confidence interval [CI], 0.60–0.98), numerically higher than that of CRP at 0.69 (95% CI, 0.55–0.84). Conclusion: Serum LRG demonstrates consistent diagnostic value in both Japanese and non-Japanese patients with IBD, supporting its broader clinical applicability across diverse populations.

Introduction: Ulcerative colitis (UC) is a diffuse, nonspecific inflammatory disease of unknown etiology. Although corticosteroids are essential for inducing remission in moderate to severe UC, steroid dependence and refractoriness remain significant clinical obstacles. Predicting which patients will develop steroid dependence or refractoriness remains challenging. Furthermore, difficult-to-treat (D-to-T) cases – those unresponsive to advanced therapies – have emerged as additional therapeutic concerns. This study aimed to identify factors associated with refractory UC, including steroid-dependent, steroid-refractory, and D-to-T presentations. Methods: A total of 216 patients with UC who received treatment at Sapporo Medical University Hospital between April 2017 and December 2023 were retrospectively analyzed. Patients were classified into four groups: steroid-naive (SN), steroid-free (SF), steroid-dependent (SD), and steroid-refractory (SR). D-to-T cases were identified within the SD and SR groups. Patient background characteristics were obtained from electronic medical records. Variables analyzed included sex, age of onset, disease duration, alcohol consumption, smoking status, disease phenotype, extraintestinal manifestations (EIMs), and cytomegalovirus (CMV) and Clostridioides difficile infection status. Results: Significant differences were observed in the prevalence of EIM and CMV reactivation across the four groups (p < 0.001 for EIM; p < 0.001 for CMV). The prevalence of EIM was significantly higher in the SR group compared with the SN group (45.5% vs. 7.7%, p = 0.002) and the SF group (45.5% vs. 4.5%, p < 0.001). CMV reactivation was more frequent in the SR group than in the SN group (36.4% vs. 1.3%, p < 0.001) and the SF group (36.4% vs. 4.5%, p < 0.004). Multivariable analysis revealed that, in comparison with the SN group, the SD group was independently associated with EIM (odds ratio [OR] = 4.59, 95% confidence interval [CI]: 1.35–15.6) and CMV reactivation (OR = 12.5, 95% CI: 1.31–119). Compared to the SF group, the SD group was associated with EIM (OR = 5.71, 95% CI: 1.44–22.7). The SR group was independently associated with EIM (OR = 12.8, 95% CI: 2.51–64.9) and CMV reactivation (OR = 65.1, 95% CI: 4.39–964) compared to the SN group. Compared to the SF group, the SR group was associated with EIM (OR = 16.4, 95% CI: 2.95–90.8) and CMV reactivation (OR = 17.0, 95% CI: 2.03–142). There are also significant associations between D-to-T status and both EIM (p < 0.01) and CMV reactivation (p = 0.037). Conclusions: Among patients with UC, the presence of EIM and CMV reactivation was significantly associated with steroid dependence, steroid refractoriness, and resistance to biologic and molecular-targeted therapies.